Airway hyperresponsiveness in FVB/N delta F508 cystic fibrosis transmembrane conductance regulator mice

Background: Airway hyperresponsiveness is a feature of clinical CF lung disease. In this study, we investigated whether the FVB/N Delta F508 CFTR mouse model has altered airway mechanics. Methods: Mechanics were measured in 12-14 week old FVB/N Cftr(tm1Eur) (Delta F508) mice and wildtype littermates using the FlexiVent small animal ventilator. Lung disease was assayed by immunohistochemistry, histology and bronchoalveolar lavage analysis. Results: Cftr(tm1Eur) mice presented with increased airway resistance, compared to wildtype littermates, in response to methacholine challenge. No differences in bronchoalveolar cell number or differential, or in tissue lymphocyte, goblet cell or smooth muscle actin levels were evident in mice grouped by Cftr genotype. The bronchoalveolar lavage of Cftr(tm1Eur) mice included significantly increased levels of interleukin 12(p40) and CXCL1 compared to controls. Conclusion: We conclude that the pulmonary phenotype of Cftr(tm1Eur) mice includes airway hyperresponsiveness in the absence of overt lung inflammation or airway remodeling. (C) 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.